Podocalyxin

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Podocalyxin
Identifiers
SymbolPODXL
PfamPF06365
InterProIPR013836
Membranome136

Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus (Bowman's capsule).[1] It is a member of the CD34 family of transmembrane sialomucins.[2] It coats the secondary foot processes of the podocytes. It is negatively charged and thus functions to keep adjacent foot processes separated, thereby keeping the urinary filtration barrier open.[3] This function is further supported by knockout studies in mice which reveal an essential role in podocyte morphogenesis[4][5] and a role in the opening of vascular lumens and regulation of vascular permeability.[6][7][8] Of note, this is the only cell surface sialomucin knockout known to display a lethal phenotype.[4] Podocalyxin is also upregulated in a number of cancers and is frequently associated with poor prognosis.[5][9][10] Sialylated, O-glycosylated glycoforms of podocalyxin expressed by colon carcinoma cells possess L-selectin and E-selectin binding activity, and may be pivotal to the metastatic spread of colon carcinoma cells.[11][12][13] At the cellular level podocalyxin has also been shown to regulate the size and topology of apical cell domains and act as a potent inducer of microvillus formation.[14]

See also[]

References[]

  1. ^ Omim - Podocalyxin-Like; Podxl
  2. ^ Nielsen JS, McNagny KM (2008). "Novel functions of the CD34 family". Journal of Cell Science. 121 (Pt 22): 3682–3692. doi:10.1242/jcs.037507. PMID 18987355.
  3. ^ Gartner, LP; Hiatt, Strum (2007). Cell Biology and Histology. Lippincott Williams and Wilkins. ISBN 978-0-7817-8577-8.
  4. ^ a b Doyonnas R, Kershaw DB, Duhme C, Merkens H, Chelliah S, Graf T, McNagny KM (2001). "Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin". J Exp Med. 194 (1): 13–27. doi:10.1084/jem.194.1.13. PMC 2193439. PMID 11435469.
  5. ^ a b Nielsen JS, McNagny KM (2009). "The role of podocalyxin in health and disease". J Am Soc Nephrol. 20 (10): 1669–76. doi:10.1681/ASN.2008070782. PMID 19578008.
  6. ^ Cait, Jessica; Hughes, Michael R.; Zeglinski, Matthew R.; Chan, Allen W.; Osterhof, Sabrina; Scott, R. Wilder; Hernaez, Diana Canals; Cait, Alissa; Vogl, A. Wayne; Bernatchez, Pascal; Underhill, T. Michael; Granville, David J.; Murphy, Timothy H.; Roskelley, Calvin D.; McNagny, Kelly M. (5 March 2019). "Podocalyxin is required for maintaining blood–brain barrier function during acute inflammation". Proceedings of the National Academy of Sciences. 116 (10): 4518–4527. doi:10.1073/pnas.1814766116. PMC 6410846. PMID 30787191.
  7. ^ Strilić, Boris; Kučera, Tomáš; Eglinger, Jan; Hughes, Michael R.; McNagny, Kelly M.; Tsukita, Sachiko; Dejana, Elisabetta; Ferrara, Napoleone; Lammert, Eckhard (October 2009). "The Molecular Basis of Vascular Lumen Formation in the Developing Mouse Aorta". Developmental Cell. 17 (4): 505–515. doi:10.1016/j.devcel.2009.08.011. PMID 19853564.
  8. ^ Debruin EJ, Hughes MR, et al. (2014). "Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion". PLOS ONE. 9 (10): e108881. Bibcode:2014PLoSO...9j8881D. doi:10.1371/journal.pone.0108881. PMC 4193771. PMID 25303643.
  9. ^ Snyder, Kimberly A; Hughes, Michael R; Hedberg, Bradley; Brandon, Jill; Hernaez, Diana Canals; Bergqvist, Peter; Cruz, Frederic; Po, Kelvin; Graves, Marcia L; Turvey, Michelle E; Nielsen, Julie S; Wilkins, John A; McColl, Shaun R; Babcook, John S; Roskelley, Calvin D; McNagny, Kelly M (27 March 2015). "Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy". Breast Cancer Research. 17 (1): 46. doi:10.1186/s13058-015-0562-7. PMC 4423095. PMID 25887862.
  10. ^ Somasiri A, Nielsen JS, Makretsov N, McCoy ML, Prentice L, Gilks CB, Chia SK, Gelmon KA, Kershaw DB, Huntsman DG, McNagny KM, Roskelley CD (2004). "Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression". Cancer Res. 64 (15): 5068–73. doi:10.1158/0008-5472.CAN-04-0240. hdl:1807.1/116. PMID 15289306. S2CID 15399303.
  11. ^ Thomas SN, Schnaar RL, Konstantopoulos K (Mar 2009). "Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells". Am J Physiol Cell Physiol. 296 (3): C505–13. doi:10.1152/ajpcell.00472.2008. PMC 2660269. PMID 19118161.
  12. ^ Konstantopoulos K, Thomas SN (2009). "Cancer cells in transit: the vascular interactions of tumor cells". Annu Rev Biomed Eng. 11: 177–202. doi:10.1146/annurev-bioeng-061008-124949. PMID 19413512.
  13. ^ Thomas SN, Tong Z, Stebe KJ, Konstantopoulos K (2009). "Identification, characterization and utilization of tumor cell selectin ligands in the design of colon cancer diagnostics". Biorheology. 46 (3): 207–25. doi:10.3233/BIR-2009-0534. PMID 19581728.
  14. ^ Nielsen JS, Graves ML, Chelliah S, Vogl AW, Roskelley CD, McNagny KM (2007). "The CD34-related molecule podocalyxin is a potent inducer of microvillus formation". PLOS ONE. 2 (2): e237. Bibcode:2007PLoSO...2..237N. doi:10.1371/journal.pone.0000237. PMC 1796660. PMID 17311105.


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